线粒体钙单向转运体拮抗剂钌红对阿霉素肾病模型大鼠的保护作用  

The protective effects of Ruthenium Red,a mitochondrial calcium uniporter antagonist,on adriamycin-induced nephropathy in rat

作　　者：许晗 管娜[1] 任雅丽[1] 魏骐骄 刘晓雅[1] 陶迎红[1] XU Han;GUAN Na;REN Ya-li;WEI Qi-jiao;LIU Xiao-ya;TAO Ying-hong(Department of Pediatrics,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院儿科,北京100034

出　　处：《中国预防医学杂志》2018年第7期481-485,共5页Chinese Preventive Medicine

基　　金：国家自然科学基金(81570639)

摘　　要：目的探讨钌红(ruthenium red,RR)对阿霉素大鼠肾病模型肾脏病理的改善作用及可能机制。方法32只SD大鼠分生理盐水对照组、RR对照组、阿霉素(adriamycin,ADR)组和ADR+RR组。予以尾静脉注射1次ADR建立大鼠肾病模型,分别予RR对照组和ADR+RR组腹腔注射RR 2周。在ADR注射后6周处死大鼠,分析RR对肾小球病变的保护作用。进而在体外培养的小鼠足细胞系分析RR对ADR诱导的足细胞凋亡和线粒体Ca^(2+)的影响。结果与ADR组比较,ADR+RR组大鼠肾小球新月体样病变指数降低(P=0.024)。与ADR组足细胞比较,ADR+RR组小鼠足细胞凋亡率降低(3.23%±0.95%vs13.62%±0.92%,P=0.028,n=3),线粒体Ca^(2+)降低(P=0.000,n=12)。结论线粒体钙单向转运体拮抗剂钌红可显著改善ADR肾病模型大鼠肾脏病理改变,拮抗ADR诱导的小鼠足细胞线粒体Ca^(2+)超载和足细胞凋亡。Objective To explore the protective effects of Ruthenium Red（RR）on adriamycin（ADR）-induced nephropathy in rat model and the possible underlying mechanism as well. Methods Thirty-two Sprague Dawley rats were divided into four groups including normal saline control（Ctl）group,RR control group,ADR group,and ADR plus RR group.Rats in ADR and ADR plus RR group were injected ADR by tail vein once to induce nephropathy.Then,rats in RR and ADR plus RR group were injected with RR intraperitoneally for 2 weeks,and other rats were injected NS as controls.6 weeks after ADR injection,all rats were sacrificed;renal cortex was collected from each rat.The protective effects of RR on renal pathology in ADR-induced nephropathy were evaluated.The in-vitro effects of RR on ADR-induced apoptosis and mitochondrial Ca（2＋）of cultured mouse podocytes were further investigated. Results The glomerular crescent like lesion index score in rats in ADR plus RR group decreased significantly compared with those in ADR group（P=0.024）.In cultured mouse podocytes,the apoptosis rates of RR pre-treated podocytes was much lower compared with ADR alone treated podocytes,the difference was statistically significant（3.23% ± 0.95% vs13.62% ±0.92%,P=0.028,n=3）,accompanied by significant decrease of mitochondrial Ca（2＋）（P=0.000,n=12）. Conclusions RR,a mitochondrial calcium uniporter inhibitor can significantly improve the glomerular pathological change induced by ADR,and it can also prevent the apoptosis and mitochondrial Ca（2＋）overloading of mouse podocytes induced by ADR.

关 键 词：局灶节段性肾小球硬化 病理 钌红 足细胞 凋亡 线粒体 钙 

分 类 号：R692[医药卫生—泌尿科学]